HWL-088 is a port-active fast linker 1 (FFA1/GPR40) agonist (EC50 of 18.9 nM) with moderate PPARδ activity (EC50 of 570.9 nM). HWL-088 improves jointing and dependence and has anti-diabetic effects.

Physicochemical Properties

Molecular Formula	C22H19FO4
Molecular Weight	366.382
Exact Mass	366.126
CAS #	2378617-96-8
PubChem CID	139600331
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	523.7±45.0 °C at 760 mmHg
Flash Point	270.5±28.7 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.591
LogP	5.23
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	7
Heavy Atom Count	27
Complexity	471
Defined Atom Stereocenter Count	0
InChi Key	NJYJBYPNDWNZAH-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H19FO4/c1-15-5-2-3-8-19(15)17-7-4-6-16(11-17)13-26-18-9-10-21(20(23)12-18)27-14-22(24)25/h2-12H,13-14H2,1H3,(H,24,25)
Chemical Name	2-[2-fluoro-4-[[3-(2-methylphenyl)phenyl]methoxy]phenoxy]acetic acid
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Insulin secretion in MIN6 cells was considerably increased by HWL-088 (0.3 μM and 3 μM) at a concentration of 25 mM, but not at a glucose concentration of 2 mM. With 25 mM glucose present, HWL-088 exhibits dose-dependent insulinotropic effects [2].
ln Vivo	HWL-088 (40 mg/kg; oral gavage; daily; for 30 days; ob/ob mice) therapy enhances beta-cell activity and lowers fat formation in adipose tissue through overexpression of pancreaticoduodenal homeobox-1 , alleviates fatty liver disease in ob/ob mice. The benefits of HWL-088 include lowering hepatic lipogenesis and oxidative stress, boosting lipoprotein lipolysis, glucose absorption, mitochondrial activity, and fatty acid beta-oxidation [2].
Animal Protocol	Animal/Disease Models: Male ob/ob mice [2] Doses: 40 mg/kg Route of Administration: po (oral gavage); daily; continued for 30 days Experimental Results: Improved β-cell function through upregulation of pancreaticoduodenal homeobox-1 , reduce fat accumulation in adipose tissue and alleviate fatty liver disease in ob/ob mice.
References	[1]. Discovery of HWL-088: A highly potent FFA1/GPR40 agonist bearing a phenoxyacetic acid scaffold. Bioorg Chem. 2019 Nov;92:103209. [2]. HWL-088, a new potent free fatty acid receptor 1 (FFAR1) agonist, improves glucolipid metabolism and acts additively with metformin in ob/ob diabetic mice. Br J Pharmacol. 2020 May;177(10):2286-2302.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~682.35 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.08 mg/mL (5.68 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.68 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7294 mL	13.6470 mL	27.2941 mL
	5 mM	0.5459 mL	2.7294 mL	5.4588 mL
	10 mM	0.2729 mL	1.3647 mL	2.7294 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.